Huckleberry lutein capsule and preparation method thereof
Through esterification reaction and capsule integration technology, the problems of lutein being easy to oxidize and not easily absorbed were solved, and vinca lutein capsules were prepared, which improved the antioxidant ability and bioavailability of lutein and achieved safe and efficient lutein supplementation.
Patent Information
- Application Number
- CN202510631273.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-05-16
- Publication Date
- 2025-07-04
AI Technical Summary
Lutein is easy to oxidize and not easily absorbed. The existing lutein supplements have low bioavailability and poor anthocyanins stability, making it difficult to achieve therapeutic effects.
Through the esterification reaction, the cinnamon extract is combined with the necessary amino acids and thiol-containing amino acids to form the cinnamon complex, and then reacts with lutein under alkaline conditions to form the cinnamon lutein complex, and incorporation is used to prepare cinnamon lutein capsules.
It improves the antioxidant ability and water solubility of lutein, enhances its bioavailability, ensures stability and safety, and promotes the absorption and release of lutein.
Smart Images
Figure BDA0005405374570000081
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of food, and particularly relates to a bilberry lutein capsule and a preparation method thereof. Background Art
[0002] Lutein belongs to carotenoid tetraterpenoid compounds. Its molecular structure is a polyene chain containing 40 carbon atoms. There are 11 conjugated double bonds on the chain, and two different ionone rings at both ends of the carbon chain. The unsaturation in the structure makes lutein less stable, and the conjugated double bonds therein are prone to oxidation, hydrolysis or isomerization under the influence of factors such as heat, light, oxygen, and acidity. Lutein has preventive and therapeutic effects on various diseases. Since humans and animals cannot synthesize lutein by themselves and can only obtain it from the outside, the abundance of lutein in food is low and it is difficult to reach the therapeutic dose. Moreover, for oral lutein supplements, because lutein is a fat-soluble substance, its bioavailability is low. Therefore, how to improve the antioxidant ability and water solubility of lutein is the key to breaking through the bottleneck of the market application of lutein. Lutein is often formulated with anthocyanins to make up for their respective deficiencies. Bilberry is rich in phenolic compounds, and anthocyanins account for nearly 90% of the total phenolic content in bilberry fruits. Combining bilberry extract with lutein has good application prospects, but anthocyanins are also easily affected by external factors in terms of their stability. Summary of the Invention
[0003] The present invention mainly provides a bilberry lutein capsule and a preparation method thereof to overcome the problems in the prior art that anthocyanins and lutein are easily oxidized and lutein is not easily absorbed. The technical solution is as follows:
[0004] A preparation method of a bilberry lutein capsule is to carry out an esterification reaction on a bilberry extract with essential amino acids and sulfur-containing amino acids, so that the carboxyl group on the amino acid combines with the phenolic hydroxyl group to obtain a bilberry complex; react the bilberry complex with lutein under alkaline conditions so that the sulfhydryl group combines with the double bond on lutein to obtain a bilberry lutein complex, and encapsulate it with a capsule to obtain a bilberry lutein capsule.
[0005] Further, the essential amino acids include one or more of leucine, isoleucine, lysine, methionine, phenylalanine, threonine or tryptophan; the sulfur-containing amino acids include one or two of cysteine or ergothioneine.
[0006] Further, the mass ratio of the essential amino acids to the sulfur-containing amino acids is 15 - 25:1; the mass ratio of the bilberry extract to the essential amino acids is 1:1.2 - 1.8; the mass ratio of the bilberry extract to lutein is 30 - 55:1.
[0007] Further, the preparation of the bilberry complex comprises the following steps: dissolving the bilberry extract and the amino acid containing a sulfhydryl group in water completely, adding dimethylaminopyridine and N,N'-dicyclohexylcarbodiimide under an inert gas atmosphere, and reacting at 3-10°C for 10-14 h; filtering, taking the filtrate, removing the dimethylaminopyridine therein with cyclohexane, and drying to obtain the bilberry complex.
[0008] Further, the mass ratio of the dimethylaminopyridine to the bilberry extract is 0.2-0.3:1; the mass ratio of the N,N'-dicyclohexylcarbodiimide to the bilberry extract is 0.3-0.45:1.
[0009] Further, it comprises the following steps: placing the bilberry complex in an aqueous solution of ethanol, adjusting the pH to weakly alkaline, adding lutein, mixing evenly, reacting at 20-35°C for 4-6 h, removing ethanol under negative pressure to obtain a solution containing the bilberry-lutein complex; adding zinc gluconate to the solution, mixing well, evaporating the solvent, and encapsulating with capsules to obtain the bilberry-lutein capsules.
[0010] Further, the volume concentration of ethanol in the aqueous solution of ethanol is 30-60%; the pH is adjusted to 7.5-9.
[0011] Further, the mass ratio of the bilberry-lutein complex to the zinc gluconate is 9-20:1.
[0012] A bilberry-lutein capsule prepared by the above preparation method has a proanthocyanidin content of not less than 8 mg / g; a lutein content of not less than 1 mg / g.
[0013] Further, the excipients include one or more of soybean oil, beeswax, gelatin, purified water or glycerol, and one or two of ferric oxide brown and titanium dioxide.
[0014] Adopting the above scheme, the method of the present invention has the following advantages:
[0015] 1. The present invention uses amino acids with high biosafety to modify and protect anthocyanins and lutein, and will not have adverse effects on the human body after taking, which is safe and effective. First, esterification is carried out to consume carboxyl groups, and then the double bond on lutein is protected by using amino groups and sulfhydryl groups, reducing the generation of side reactions.
[0016] 2. The present invention uses the phenolic hydroxyl group on anthocyanins in the bilberry extract to esterify with the carboxyl group in the amino acid to protect the phenolic hydroxyl group and improve its antioxidant ability. Moreover, the combination of the two is reversible and can be gradually decomposed in the human body environment without affecting absorption. At the same time, after the ester group decomposes, anthocyanins can still be connected to lutein through the electrostatic interaction between the oxonium group and the phenolic hydroxyl group to protect lutein.
[0017] 3. The present invention utilizes amino acids to combine anthocyanidins and lutein, thereby increasing the volume of the obtained complex, surrounding the lutein with anthocyanidins, exposing less reactive sites, making it less susceptible to the external environment, and having high storage stability.
[0018] 4. The present invention combines anthocyanidins with lutein through sulfhydryl-containing amino acids, and the highly water-soluble anthocyanidins surround the lutein, which promotes the dispersion of lutein, improves the water solubility of lutein, and makes it easier to absorb. Lutein and anthocyanidins form small molecule micelles, which reduces the oxidation of lutein and improves its bioaccessibility.
[0019] 5. The present invention utilizes the nucleophilic amino group and the more active thiol group in the amino acid to perform nucleophilic addition with the active site in the conjugated double bond system of lutein, thereby avoiding the oxidation of the double bond. The reaction process is mild, and the thiol group is easy to leave, which has little effect on the activity of lutein and has strong practicality.
[0020] 6. After the blueberry lutein complex is prepared, the present invention mixes it with zinc gluconate in water, and utilizes the property that sulfur is more likely to donate electrons than oxygen, so that zinc ions are more easily attracted around the sulfur of the amino acid, further weakening the binding stability of the double bond between sulfur and lutein, making it easier to decompose after entering the human body. DETAILED DESCRIPTION
[0021] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0022] Example 1: (1) 5 g of bilberry extract, 5 g of leucine, 2.5 g of lysine and 0.5 g of cysteine were fully dissolved in water, and 1.2 g of dimethylaminopyridine and 2 g of N,N-dicyclohexylcarboximide were added under an inert gas atmosphere, and reacted at 6° C. for 12 h; filtered, and the filtrate was taken to remove dimethylaminopyridine with cyclohexane, and dried to obtain a bilberry complex;
[0023] (2) The prepared bilberry complex was placed in 50% v / v ethanol, the pH was adjusted to 8, 0.13 g of lutein was added, the mixture was mixed well, and the mixture was reacted at 30° C. for 5 h, and the ethanol was removed under negative pressure to obtain a solution containing the bilberry lutein complex; 0.8 g of zinc gluconate was added to the solution, the mixture was mixed well, and the solvent was evaporated to obtain the bilberry lutein complex;
[0024] (3) Sieve the bilberry lutein complex, soybean oil, beeswax, gelatin, glycerol, ferric oxide brown, and titanium dioxide; take 10 g of the bilberry lutein complex, 1 g of beeswax, and 18 g of soybean oil, mix and homogenize them as the content; take 6 g of gelatin, 3 g of glycerol, 1 mg of ferric oxide brown, and 1 mg of titanium dioxide, mix them to form a uniform colloidal solution, and obtain 50 bilberry lutein capsules through pill pressing and drying.
[0025] Example 2: The difference from Example 1 is that:
[0026] (1) Dissolve 5 g of bilberry extract, 5 g of leucine, 2.5 g of lysine, and 0.3 g of cysteine in water completely. Under an inert gas atmosphere, add 1.2 g of dimethylaminopyridine and 2 g of N,N'-dicyclohexylcarbodiimide, and react at 5 °C for 12 h; filter, take the filtrate, remove the dimethylaminopyridine in it with cyclohexane, and obtain the bilberry complex after drying.
[0027] Example 3: The difference from Example 1 is that:
[0028] (1) Dissolve 5 g of bilberry extract, 5 g of leucine, 2.5 g of lysine, and 0.5 g of cysteine in water completely. Under an inert gas atmosphere, add 1.2 g of dimethylaminopyridine and 2 g of N,N'-dicyclohexylcarbodiimide, and react at 3 °C for 12 h; filter, take the filtrate, remove the dimethylaminopyridine in it with cyclohexane, and obtain the bilberry complex after drying.
[0029] Example 4: The difference from Example 1 is that:
[0030] (1) Dissolve 5 g of bilberry extract, 5 g of leucine, 2.5 g of lysine, and 0.5 g of cysteine in water completely. Under an inert gas atmosphere, add 1.2 g of dimethylaminopyridine and 2 g of N,N'-dicyclohexylcarbodiimide, and react at 10 °C for 12 h; filter, take the filtrate, remove the dimethylaminopyridine in it with cyclohexane, and obtain the bilberry complex after drying.
[0031] Example 5: The difference from Example 1 is that:
[0032] (2) Put the prepared bilberry complex into 30% v / v ethanol, adjust the pH to 8, add 0.13 g of lutein, mix evenly and react at 30 °C for 5 h, remove the ethanol under negative pressure to obtain a solution containing the bilberry lutein complex; add 0.8 g of zinc gluconate to the solution, mix well, and evaporate the solvent to obtain the bilberry lutein complex.
[0033] Example 6: The difference from Example 1 is that:
[0034] (2) The prepared bilberry complex was placed in ethanol with a concentration of 50% v / v, the pH was adjusted to 9, 0.13 g of lutein was added, and after mixing evenly, the reaction was carried out at 30 °C for 5 h. Ethanol was removed under negative pressure to obtain a solution containing the bilberry-lutein complex. 0.8 g of zinc gluconate was added to the solution, mixed thoroughly, and the solvent was evaporated to dryness to obtain the bilberry-lutein complex.
[0035] Example 7: The difference from Example 1 is that:
[0036] (2) The prepared bilberry complex was placed in ethanol with a concentration of 50% v / v, the pH was adjusted to 8, 0.13 g of lutein was added, and after mixing evenly, the reaction was carried out at 20 °C for 6 h. Ethanol was removed under negative pressure to obtain a solution containing the bilberry-lutein complex. 0.8 g of zinc gluconate was added to the solution, mixed thoroughly, and the solvent was evaporated to dryness to obtain the bilberry-lutein complex.
[0037] Comparative Example 1: The difference from Example 1 is that:
[0038] (1) 5 g of bilberry extract, 5 g of leucine, 2.5 g of lysine and 0.5 g of cysteine were placed in water and dissolved thoroughly. Under an inert gas atmosphere, 1.2 g of dimethylaminopyridine and 2 g of N,N'-dicyclohexylcarbodiimide were added, and the reaction was carried out at 5 °C for 12 h; after filtration, the filtrate was taken and the dimethylaminopyridine in it was removed with cyclohexane, and after drying, the bilberry complex was obtained;
[0039] (2) The bilberry-lutein complex, soybean oil, beeswax, gelatin, glycerol, ferric oxide brown and titanium dioxide were sieved; 10 g of the bilberry-lutein complex, 0.13 g of lutein, 0.8 g of zinc gluconate, 1 g of beeswax and 18 g of soybean oil were taken and homogenized as the content; 6 g of gelatin, 3 g of glycerol, 1 mg of ferric oxide brown and 1 mg of titanium dioxide were taken and mixed to form a uniform colloidal solution, which was made into pills by pressing and dried to obtain 50 bilberry-lutein capsules.
[0040] Comparative Example 2: The difference from Example 1 is that:
[0041] (2) The prepared bilberry complex was placed in ethanol with a concentration of 50% v / v, the pH was adjusted to 8, 0.13 g of lutein was added, and after mixing evenly, the reaction was carried out at 30 °C for 5 h. Ethanol was removed under negative pressure to obtain a solution containing the bilberry-lutein complex, and the solvent was evaporated to dryness to obtain the bilberry-lutein complex.
[0042] Testing of example samples:
[0043] Determination of proanthocyanidins: Extrude the contents of 20 soft capsules as much as possible. Weigh an appropriate amount of the sample and place it in a small beaker, stir it several times with 20 mL of methanol to wash the proanthocyanidins into a 50 mL volumetric flask until the methanol extract is colorless, add methanol to the scale, and shake well.
[0044] Weigh 10.0 mg of the proanthocyanidin standard product and dissolve it in 10 mL of methanol. Pipette 0, 0.1, 0.25, 0.5, 1.0, and 1.5 mL of this solution into 10-mL volumetric flasks, add methanol to the mark, and mix well. Take 1 mL from each flask for determination and plot the standard curve.
[0045] Mix n-butanol and hydrochloric acid in a volume ratio of 95:5. Take out 6 mL and place it in a stoppered conical flask. Then add 0.2 mL of ammonium ferric sulfate solution and 1 mL of the sample solution, mix well, place it in a boiling water bath for reflux, heat precisely for 40 min, immediately cool it in ice water. After 15 min from the end of heating, measure the absorbance at a wavelength of 546 nm, and calculate the content of proanthocyanidin in the sample from the standard curve. The color development is stable within 1 hour.
[0046] In vitro digestion experiment: Take one capsule and place it in 5 mL of water. Add 1 mL of Tween-40, dry the solution at 35 °C, then successively add 5 mL of normal saline, 5 mL of human electrolyte, and 5 mL of 40 mg / mL pepsin solution. Make up the volume to 25 mL with normal saline, then adjust the pH value to 2.0 with dilute hydrochloric acid, seal it and keep it away from light, shake it at 150 r / min in a 37 °C water bath for 60 min, take samples to measure the absorbance value of lutein in the simulated gastric digestive juice, and analyze the release rate; adjust the pH value to 5.3 with dilute NaOH solution, add 8 mL of trypsin solution, then slowly adjust the pH value to 7.0 with dilute NaOH solution, continue to shake for 120 min, take samples to measure and analyze the release rate of lutein in the simulated intestinal digestive juice. Then take samples for the DPPH free radical scavenging experiment, and after the experiment is completed, measure the DPPH free radical scavenging rate.
[0047] Table 1:
[0048]
[0049] During the preparation process, the amount of cysteine participating in the reaction in Example 2 was less than that in Example 1. The release rate of lutein in the simulated gastric juice environment was greater, while the release rate in the simulated intestinal juice decreased. Compared with Comparative Example 1 without cysteine modification, the gastrointestinal release rates of Example 2 were significantly higher than those of Comparative Example 1, indicating that cysteine modification can improve the solubility of lutein and increase the release rate. However, a decrease in the degree of cysteine modification would lead to a decrease in its protection of lutein, resulting in a decrease in its release rate in the intestinal juice environment. It is possible that the released lutein was oxidized and modified to a certain extent, affecting the content of lutein. The temperature of the esterification reaction in Example 3 was lower than that in Example 1, and the temperature in Example 4 was higher. However, the release rate of lutein in Example 3 decreased, and the content of proanthocyanidins in Example 4 decreased. The free radical scavenging rates of both decreased. It may be that a lower temperature is not conducive to the full progress of esterification, and excessive carboxyl groups in the amino group affect the complexation of amino acids and lutein. A higher temperature may increase side reactions, affecting the content of proanthocyanidins.
[0050] When complexing lutein with bilberry complex, the content of solvent ethanol in Example 5 was reduced compared with Example 1. The release rates of lutein in gastric juice and intestinal juice decreased, and the free radical scavenging rate also decreased, indicating that the reduction of ethanol affected the binding of lutein and amino acids and would also cause the rapid evaporation of ethanol, making lutein easily damaged. The reaction pH value in Example 6 was higher, and the release rate of lutein and the free radical scavenging rate also decreased significantly, indicating that a higher pH is not conducive to the stable progress of the reaction and is also not conducive to the release of lutein. The reaction temperature in Example 7 was low, but the time was longer. The release rate of lutein decreased compared with Example 1, but the change was not obvious, indicating that the reaction can proceed smoothly by extending the reaction time at a low temperature, but extending the time also means an increase in cost. Comparative Example 2 did not use zinc gluconate for treatment, and the release rate of lutein decreased significantly, indicating that zinc gluconate is helpful for the release of lutein.
[0051] For those skilled in the art, various corresponding changes and deformations can be made according to the technical solutions and concepts described above, and all such changes and deformations should fall within the protection scope of the claims of the present invention.
Claims
1. A preparation method of bilberry lutein capsules, characterized in that, The esterification reaction is carried out on the bilberry extract with essential amino acids and sulfur-containing amino acids, so that the carboxyl group on the amino acid combines with the phenolic hydroxyl group to obtain a bilberry complex; the bilberry complex reacts with lutein under alkaline conditions, so that the sulfhydryl group combines with the double bond on lutein to obtain a bilberry lutein complex, which is encapsulated with capsules to obtain bilberry lutein capsules.
2. The preparation method of the bilberry lutein capsules according to claim 1, characterized in that, The essential amino acids include one or more of leucine, isoleucine, lysine, methionine, phenylalanine, threonine or tryptophan; the sulfur-containing amino acids include one or two of cysteine or ergothioneine.
3. The preparation method of the bilberry lutein capsule according to claim 2, characterized in that, The mass ratio of the essential amino acids to the sulfur-containing amino acids is 15-25:1; the mass ratio of the bilberry extract to the essential amino acids is 1:1.2-1.8; the mass ratio of the bilberry extract to lutein is 30-55:
1.
4. The preparation method of the bilberry lutein capsules according to claim 1, characterized in that, The preparation of the bilberry complex includes the following steps: The bilberry extract and the sulfur-containing amino acids are placed in water and fully dissolved. Under an inert gas atmosphere, dimethylaminopyridine and N,N-dicyclohexylcarbodiimide are added, and the reaction is carried out at 3-10 °C for 10-14 h; filtered, and the filtrate is taken to remove the dimethylaminopyridine therein with cyclohexane, and the bilberry complex is obtained after drying.
5. The preparation method of the bilberry lutein capsule according to claim 4, characterized in that, The mass ratio of dimethylaminopyridine to the bilberry extract is 0.2-0.3:1; the mass ratio of N,N-dicyclohexylcarbodiimide to the bilberry extract is 0.3-0.45:
1.
6. The preparation method of the bilberry lutein capsules according to claim 1, characterized in that, It includes the following steps: The bilberry complex is placed in an aqueous solution of ethanol, the pH is adjusted to weakly alkaline, lutein is added, and after mixing evenly, the reaction is carried out at 20-35 °C for 4-6 h, and ethanol is removed under negative pressure to obtain a solution containing the bilberry lutein complex; zinc gluconate is added to the solution, fully mixed, the solvent is evaporated to dryness, and encapsulated with capsules to obtain bilberry lutein capsules.
7. The preparation method of the bilberry lutein capsules according to claim 6, characterized in that, The volume concentration of ethanol in the aqueous solution of ethanol is 30-60%; the pH is adjusted to 7.5-9.
8. The preparation method of the bilberry lutein capsules according to claim 6, wherein The mass ratio of the bilberry lutein complex to zinc gluconate is 9-20:
1.
9. A bilberry lutein capsule prepared by the preparation method according to any one of claims 1 to 8, characterized in that, The content of proanthocyanidins is not less than 8 mg / g; the content of lutein is not less than 1 mg / g.
10. The bilberry lutein capsules according to claim 9, characterized in that, The excipients include one or more of soybean oil, beeswax, gelatin, purified water or glycerol, and one or two of ferric oxide brown and titanium dioxide.